Cell therapy for full-thickness wounds: are fetal dermal cells a potential source?

J J Akershoek,B K H L Boekema,M M W Ulrich,W Talhout,C D Richters,M Vlig,K M Brouwer,R H J Beelen,E Middelkoop

doi:10.1007/s00441-015-2293-6

Abstract

The application of autologous dermal fibroblasts has been shown to improve burn wound healing. However, a major hurdle is the availability of sufficient healthy skin as a cell source. We investigated fetal dermal cells as an alternative source for cell-based therapy for skin regeneration. Human (hFF), porcine fetal (pFF) or autologous dermal fibroblasts (AF) were seeded in a collagen–elastin substitute (Novomaix, NVM), which was applied in combination with an autologous split thickness skin graft (STSG) to evaluate the effects of these cells on wound healing in a porcine excisional wound model. Transplantation of wounds with NVM+hFF showed an increased influx of inflammatory cells (e.g., neutrophils, macrophages, CD4+ and CD8+ lymphocytes) compared to STSG, acellular NVM (Acell-NVM) and NVM+AF at post-surgery days 7 and/or 14. Wounds treated with NVM+pFF presented only an increase in CD8+ lymphocyte influx. Furthermore, reduced alpha-smooth muscle actin (αSMA) expression in wound areas and reduced contraction of the wounds was observed with NVM+AF compared to Acell-NVM. Xenogeneic transplantation of NVM+hFF increased αSMA expression in wounds compared to NVM+AF. An improved scar quality was observed for wounds treated with NVM+AF compared to Acell-NVM, NVM+hFF and NVM+pFF at day 56. In conclusion, application of autologous fibroblasts improved the overall outcome of wound healing in comparison to fetal dermal cells and Acell-NVM, whereas application of fetal dermal fibroblasts in NVM did not improve wound healing of full-thickness wounds in a porcine model. Although human fetal dermal cells demonstrated an increased immune response, this did not seem to affect scar quality.

Highlights

Deep partial and full-thickness burn wounds often result in hypertrophic scars
Examples of this have been described by Bloemen et al (2010) and Ryssel et al (2008), who showed that transplantation of acellular collagen-based dermal substitutes with split thickness skin grafts (STSG) on top of fullthickness burn wounds improved scar quality
autologous dermal fibroblasts (AF), hFF and pFF cultured on glass slides showed similar staining of the cytoplasm for heat shock protein 47 (HSP47) (Fig. 1d-f). αSMA expression in these cells was similar for AF and pFF; the αSMA expression in hFF seemed slightly lower (Fig. 1a-c). αSMA expression by these cells was represented as a stress fiber phenotype

Summary

Introduction

Deep partial and full-thickness burn wounds often result in hypertrophic scars. One of the causes that lead to hypertrophic scarring of burn wounds is partial or complete loss of the dermis. The use of collagen-based dermal substitutes to replace the lost and/or damaged dermis has been shown to improve the outcome of wound healing. Examples of this have been described by Bloemen et al (2010) and Ryssel et al (2008), who showed that transplantation of acellular collagen-based dermal substitutes with split thickness skin grafts (STSG) on top of fullthickness burn wounds improved scar quality. Despite improved scar quality when using acellular dermal substitutes, the optimal result of full skin regeneration is still not achieved. Cell-based therapy is one of the strategies that may further improve skin

Objectives

Methods

Results

Discussion

Conclusion